CA2269943C - Method for the production of ivermectin - Google Patents

Method for the production of ivermectin Download PDF

Info

Publication number: CA2269943C
Authority: CA; Canada
Prior art keywords: alkyl; phosphine; ivermectin; rhodium; phosphines
Prior art date: 1996-10-31
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA002269943A

Other languages

English (en)

French (fr)

Other versions

CA2269943A1 (en

Inventor

Dieter Arlt

Gerhard Bonse

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bayer AG

Original Assignee

Bayer AG

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1996-10-31

Filing date

1997-10-20

Publication date

2006-12-12

1997-10-20 Application filed by Bayer AG filed Critical Bayer AG

1998-05-07 Publication of CA2269943A1 publication Critical patent/CA2269943A1/en

2006-12-12 Application granted granted Critical

2006-12-12 Publication of CA2269943C publication Critical patent/CA2269943C/en

2017-10-20 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

AZSNMRSAGSSBNP-UHFFFAOYSA-N 22,23-dihydroavermectin B1a Natural products C1CC(C)C(C(C)CC)OC21OC(CC=C(C)C(OC1OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C1)C(C)C=CC=C1C3(C(C(=O)O4)C=C(C)C(O)C3OC1)O)CC4C2 AZSNMRSAGSSBNP-UHFFFAOYSA-N 0.000 title claims abstract description 20
SPBDXSGPUHCETR-JFUDTMANSA-N 8883yp2r6d Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 SPBDXSGPUHCETR-JFUDTMANSA-N 0.000 title claims abstract description 20
229960002418 ivermectin Drugs 0.000 title claims abstract description 20
238000004519 manufacturing process Methods 0.000 title claims abstract description 6
238000000034 method Methods 0.000 title description 13
238000005984 hydrogenation reaction Methods 0.000 claims abstract description 26
239000003054 catalyst Substances 0.000 claims description 47
239000000203 mixture Substances 0.000 claims description 16
239000002904 solvent Substances 0.000 claims description 15
125000000217 alkyl group Chemical group 0.000 claims description 14
RRZXIRBKKLTSOM-XPNPUAGNSA-N avermectin B1a Chemical compound C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 RRZXIRBKKLTSOM-XPNPUAGNSA-N 0.000 claims description 12
150000003003 phosphines Chemical class 0.000 claims description 12
125000003545 alkoxy group Chemical group 0.000 claims description 10
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 6
150000003283 rhodium Chemical class 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 4
150000003284 rhodium compounds Chemical class 0.000 claims description 4
125000003710 aryl alkyl group Chemical class 0.000 claims description 2
150000002429 hydrazines Chemical class 0.000 claims description 2
239000011541 reaction mixture Substances 0.000 claims description 2
ZFUKERYTFURFGA-UHFFFAOYSA-N Avermectin B1b Natural products O1C(C)C(O)C(OC)CC1OC1C(OC)CC(OC2C(=CCC3CC(CC4(O3)C=CC(C)C(C(C)C)O4)OC(=O)C3C=C(C)C(O)C4OCC(C34O)=CC=CC2C)C)OC1C ZFUKERYTFURFGA-UHFFFAOYSA-N 0.000 claims 1
RRZXIRBKKLTSOM-UHFFFAOYSA-N avermectin B1a Natural products C1=CC(C)C(C(C)CC)OC11OC(CC=C(C)C(OC2OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C2)C(C)C=CC=C2C3(C(C(=O)O4)C=C(C)C(O)C3OC2)O)CC4C1 RRZXIRBKKLTSOM-UHFFFAOYSA-N 0.000 claims 1
ZFUKERYTFURFGA-PVVXTEPVSA-N avermectin B1b Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C ZFUKERYTFURFGA-PVVXTEPVSA-N 0.000 claims 1
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
238000000926 separation method Methods 0.000 abstract description 4
239000000047 product Substances 0.000 description 22
239000005660 Abamectin Substances 0.000 description 12
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 12
239000000243 solution Substances 0.000 description 12
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 11
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
238000000605 extraction Methods 0.000 description 9
239000010948 rhodium Substances 0.000 description 9
229910000073 phosphorus hydride Inorganic materials 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
150000001875 compounds Chemical class 0.000 description 5
239000003446 ligand Substances 0.000 description 5
229910052703 rhodium Inorganic materials 0.000 description 5
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 5
239000011877 solvent mixture Substances 0.000 description 5
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
238000001816 cooling Methods 0.000 description 4
125000005843 halogen group Chemical group 0.000 description 4
229910052751 metal Inorganic materials 0.000 description 4
239000002184 metal Substances 0.000 description 4
239000007858 starting material Substances 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
239000004215 Carbon black (E152) Substances 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
239000012043 crude product Substances 0.000 description 3
JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 3
238000004821 distillation Methods 0.000 description 3
238000001914 filtration Methods 0.000 description 3
229930195733 hydrocarbon Natural products 0.000 description 3
-1 rhodium(I) chloride dimer Chemical class 0.000 description 3
IAZVKSPSDDMXJN-UHFFFAOYSA-N tris(2-hexylphenyl)phosphane Chemical compound CCCCCCC1=CC=CC=C1P(C=1C(=CC=CC=1)CCCCCC)C1=CC=CC=C1CCCCCC IAZVKSPSDDMXJN-UHFFFAOYSA-N 0.000 description 3
XDFMLOZSDDINPW-UHFFFAOYSA-N tris(2-octylphenyl)phosphane Chemical compound CCCCCCCCC1=CC=CC=C1P(C=1C(=CC=CC=1)CCCCCCCC)C1=CC=CC=C1CCCCCCCC XDFMLOZSDDINPW-UHFFFAOYSA-N 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
IKZVAPMTXDXWMX-UHFFFAOYSA-N 2-methoxy-2,4,4-trimethylpentane Chemical compound COC(C)(C)CC(C)(C)C IKZVAPMTXDXWMX-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical class [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
229910052786 argon Inorganic materials 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
150000004696 coordination complex Chemical class 0.000 description 2
LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
229910000510 noble metal Inorganic materials 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
238000010992 reflux Methods 0.000 description 2
238000003756 stirring Methods 0.000 description 2
HSSMNYDDDSNUKH-UHFFFAOYSA-K trichlororhodium;hydrate Chemical compound O.Cl[Rh](Cl)Cl HSSMNYDDDSNUKH-UHFFFAOYSA-K 0.000 description 2
PONVJPLHMAEYCA-UHFFFAOYSA-N (2-dodecylphenyl)-diphenylphosphane Chemical compound CCCCCCCCCCCCC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 PONVJPLHMAEYCA-UHFFFAOYSA-N 0.000 description 1
SBGKCOJQKBHFTO-UHFFFAOYSA-N (2-nonylphenyl)phosphane Chemical compound CCCCCCCCCC1=CC=CC=C1P SBGKCOJQKBHFTO-UHFFFAOYSA-N 0.000 description 1
PAUKPFHSVRPCHY-UHFFFAOYSA-N (3-dodecylphenyl)-diphenylphosphane Chemical compound CCCCCCCCCCCCC1=CC=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 PAUKPFHSVRPCHY-UHFFFAOYSA-N 0.000 description 1
XASZHEOEIZZKPV-UHFFFAOYSA-N (4-dodecoxyphenyl)-diphenylphosphane Chemical compound C1=CC(OCCCCCCCCCCCC)=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 XASZHEOEIZZKPV-UHFFFAOYSA-N 0.000 description 1
GMKDBCMQUXZCMQ-UHFFFAOYSA-N (4-dodecylphenyl)-bis(2-methoxyphenyl)phosphane Chemical compound C1=CC(CCCCCCCCCCCC)=CC=C1P(C=1C(=CC=CC=1)OC)C1=CC=CC=C1OC GMKDBCMQUXZCMQ-UHFFFAOYSA-N 0.000 description 1
JEUHXCDGOOSMJU-UHFFFAOYSA-N (4-dodecylphenyl)-bis(2-methylphenyl)phosphane Chemical compound C1=CC(CCCCCCCCCCCC)=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C JEUHXCDGOOSMJU-UHFFFAOYSA-N 0.000 description 1
IQVSBYMGZNPMPY-UHFFFAOYSA-N (4-dodecylphenyl)-diphenylphosphane Chemical compound C1=CC(CCCCCCCCCCCC)=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 IQVSBYMGZNPMPY-UHFFFAOYSA-N 0.000 description 1
VZXUCNNDMVYEHZ-UHFFFAOYSA-N (4-octadecylphenyl)-diphenylphosphane Chemical compound C1=CC(CCCCCCCCCCCCCCCCCC)=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 VZXUCNNDMVYEHZ-UHFFFAOYSA-N 0.000 description 1
POILWHVDKZOXJZ-ARJAWSKDSA-M (z)-4-oxopent-2-en-2-olate Chemical compound C\C([O-])=C\C(C)=O POILWHVDKZOXJZ-ARJAWSKDSA-M 0.000 description 1
PRBHEGAFLDMLAL-UHFFFAOYSA-N 1,5-Hexadiene Natural products CC=CCC=C PRBHEGAFLDMLAL-UHFFFAOYSA-N 0.000 description 1
RFEJUZJILGIRHQ-XRIOVQLTSA-N 2,3-dihydroxybutanedioic acid;3-[(2s)-1-methylpyrrolidin-2-yl]pyridine Chemical compound OC(=O)C(O)C(O)C(O)=O.OC(=O)C(O)C(O)C(O)=O.CN1CCC[C@H]1C1=CC=CN=C1 RFEJUZJILGIRHQ-XRIOVQLTSA-N 0.000 description 1
BWDBEAQIHAEVLV-UHFFFAOYSA-N 6-methylheptan-1-ol Chemical compound CC(C)CCCCCO BWDBEAQIHAEVLV-UHFFFAOYSA-N 0.000 description 1
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
229910021604 Rhodium(III) chloride Inorganic materials 0.000 description 1
229910000831 Steel Inorganic materials 0.000 description 1
241001468227 Streptomyces avermitilis Species 0.000 description 1
230000000895 acaricidal effect Effects 0.000 description 1
239000000642 acaricide Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
230000000507 anthelmentic effect Effects 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
JJYGVZHYQOUZQX-UHFFFAOYSA-N benzyl-(2-dodecylphenyl)-phenylphosphane Chemical compound C(CCCCCCCCCCC)C1=C(C=CC=C1)P(C1=CC=CC=C1)CC1=CC=CC=C1 JJYGVZHYQOUZQX-UHFFFAOYSA-N 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
238000010352 biotechnological method Methods 0.000 description 1
YTHUMEWRJHQMKK-UHFFFAOYSA-N bis(2-dodecylphenyl)-methylphosphane Chemical compound CCCCCCCCCCCCC1=CC=CC=C1P(C)C1=CC=CC=C1CCCCCCCCCCCC YTHUMEWRJHQMKK-UHFFFAOYSA-N 0.000 description 1
VLBXMKAMXZWJDT-UHFFFAOYSA-N bis(2-hexadecylphenyl)-phenylphosphane Chemical compound CCCCCCCCCCCCCCCCC1=CC=CC=C1P(C=1C(=CC=CC=1)CCCCCCCCCCCCCCCC)C1=CC=CC=C1 VLBXMKAMXZWJDT-UHFFFAOYSA-N 0.000 description 1
GTXMHESYFUCYCG-UHFFFAOYSA-N bis(2-octadecylphenyl)-phenylphosphane Chemical compound CCCCCCCCCCCCCCCCCCC1=CC=CC=C1P(C=1C(=CC=CC=1)CCCCCCCCCCCCCCCCCC)C1=CC=CC=C1 GTXMHESYFUCYCG-UHFFFAOYSA-N 0.000 description 1
QDMFFULEGGUANK-UHFFFAOYSA-N bis(4-chlorophenyl)-(4-octadecylphenyl)phosphane Chemical compound C1=CC(CCCCCCCCCCCCCCCCCC)=CC=C1P(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 QDMFFULEGGUANK-UHFFFAOYSA-N 0.000 description 1
OBICSUJWYDBFIE-UHFFFAOYSA-N bis(4-tert-butylphenyl)-dodecan-4-ylphosphane Chemical compound C=1C=C(C(C)(C)C)C=CC=1P(C(CCC)CCCCCCCC)C1=CC=C(C(C)(C)C)C=C1 OBICSUJWYDBFIE-UHFFFAOYSA-N 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
239000012045 crude solution Substances 0.000 description 1
HOXDXGRSZJEEKN-UHFFFAOYSA-N cycloocta-1,5-diene;rhodium Chemical compound [Rh].C1CC=CCCC=C1 HOXDXGRSZJEEKN-UHFFFAOYSA-N 0.000 description 1
JQYXTEDHPQKHPF-UHFFFAOYSA-N didodecyl(phenyl)phosphane Chemical compound CCCCCCCCCCCCP(CCCCCCCCCCCC)C1=CC=CC=C1 JQYXTEDHPQKHPF-UHFFFAOYSA-N 0.000 description 1
CVXCDKGXJCMKIA-UHFFFAOYSA-N didodecyl-[2-[4-(trifluoromethyl)phenyl]phenyl]phosphane Chemical compound FC(C1=CC=C(C=C1)C1=C(C=CC=C1)P(CCCCCCCCCCCC)CCCCCCCCCCCC)(F)F CVXCDKGXJCMKIA-UHFFFAOYSA-N 0.000 description 1
KCYMAYAYGICFGX-UHFFFAOYSA-N dodecyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(CCCCCCCCCCCC)C1=CC=CC=C1 KCYMAYAYGICFGX-UHFFFAOYSA-N 0.000 description 1
239000013057 ectoparasiticide Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
229910001385 heavy metal Inorganic materials 0.000 description 1
PYGSKMBEVAICCR-UHFFFAOYSA-N hexa-1,5-diene Chemical compound C=CCCC=C PYGSKMBEVAICCR-UHFFFAOYSA-N 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000002917 insecticide Substances 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000000463 material Substances 0.000 description 1
GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000004064 recycling Methods 0.000 description 1
SONJTKJMTWTJCT-UHFFFAOYSA-K rhodium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Rh+3] SONJTKJMTWTJCT-UHFFFAOYSA-K 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000010959 steel Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
WMUVAMXULTVKIW-UHFFFAOYSA-K tribromorhodium;hydrate Chemical compound O.Br[Rh](Br)Br WMUVAMXULTVKIW-UHFFFAOYSA-K 0.000 description 1
ZCVZUHKHDDIKJF-UHFFFAOYSA-N tris(2-decylphenyl)phosphane Chemical compound CCCCCCCCCCC1=CC=CC=C1P(C=1C(=CC=CC=1)CCCCCCCCCC)C1=CC=CC=C1CCCCCCCCCC ZCVZUHKHDDIKJF-UHFFFAOYSA-N 0.000 description 1
UQHFPPSBVOIUFM-UHFFFAOYSA-N tris(4-tert-butylphenyl)phosphane Chemical compound C1=CC(C(C)(C)C)=CC=C1P(C=1C=CC(=CC=1)C(C)(C)C)C1=CC=C(C(C)(C)C)C=C1 UQHFPPSBVOIUFM-UHFFFAOYSA-N 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
UTODFRQBVUVYOB-UHFFFAOYSA-P wilkinson's catalyst Chemical compound [Cl-].C1=CC=CC=C1P(C=1C=CC=CC=1)(C=1C=CC=CC=1)[Rh+](P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 UTODFRQBVUVYOB-UHFFFAOYSA-P 0.000 description 1
239000011995 wilkinson's catalyst Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Molecular Biology (AREA)
Life Sciences & Earth Sciences (AREA)
Biochemistry (AREA)
Biotechnology (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Steroid Compounds (AREA)
Compounds Of Unknown Constitution (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

CA002269943A 1996-10-31 1997-10-20 Method for the production of ivermectin Expired - Fee Related CA2269943C (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DE19644050A DE19644050A1 (de)	1996-10-31	1996-10-31	Verfahren zur Herstellung von Ivermectin
DE19644050.5		1996-10-31
PCT/EP1997/005777 WO1998018806A1 (de)	1996-10-31	1997-10-20	Verfahren zur herstellung von ivermectin

Publications (2)

Publication Number	Publication Date
CA2269943A1 CA2269943A1 (en)	1998-05-07
CA2269943C true CA2269943C (en)	2006-12-12

Family

ID=7809764

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002269943A Expired - Fee Related CA2269943C (en)	1996-10-31	1997-10-20	Method for the production of ivermectin

Country Status (15)

Country	Link
US (1)	US6072052A (de)
EP (1)	EP0937094B1 (de)
JP (1)	JP2001502716A (de)
KR (1)	KR100468206B1 (de)
CN (1)	CN1146572C (de)
AT (1)	ATE215552T1 (de)
AU (1)	AU5051298A (de)
BR (1)	BR9712690A (de)
CA (1)	CA2269943C (de)
DE (2)	DE19644050A1 (de)
DK (1)	DK0937094T3 (de)
ES (1)	ES2175377T3 (de)
HU (1)	HUP9904497A3 (de)
PT (1)	PT937094E (de)
WO (1)	WO1998018806A1 (de)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE19644050A1 (de) *	1996-10-31	1998-05-07	Bayer Ag	Verfahren zur Herstellung von Ivermectin
CN100396691C (zh) *	2004-12-06	2008-06-25	四川大学	一种伊维菌素的制备方法
PT117268B (pt)	2021-06-01	2023-12-05	Hovione Farm S A	Processo para controlar o tamanho de partícula e substâncias aparentadas da ivermectina com utilização de alto cisalhamento

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PH15982A (en) *	1977-10-03	1983-05-18	Merck & Co Inc	Selective hydrogenation producta of c-076 compounds and derivatives thereof
US4413118A (en) *	1981-03-02	1983-11-01	Merck & Co., Inc.	Process for removal of homogeneous catalyst group VIII metals from process streams
PT74303B (fr) *	1982-01-19	1983-08-08	Joao Emerico Villax	Procede pour la preparation de nouveaux catalysateurs contenant rhodium et son utilisation
US4550096A (en) *	1982-01-19	1985-10-29	Plurichemie Anstalt	Homogeneous catalytic system comprising rhodium, hydrazine and phosphine and a process for the preparation of same
GB2114627B (en) *	1982-02-09	1985-05-01	Padley And Venables Limited	Mineral mining apparatus provided with dust suppressing means
DE19507018A1 (de) *	1995-03-01	1996-09-05	Bayer Ag	Verfahren zur Herstellung von Ivermectin
DE19644050A1 (de) *	1996-10-31	1998-05-07	Bayer Ag	Verfahren zur Herstellung von Ivermectin
IT1289993B1 (it) *	1997-02-27	1998-10-19	Antibioticos Spa	Processo per la preparazione di ivermectina

1996
- 1996-10-31 DE DE19644050A patent/DE19644050A1/de not_active Withdrawn
1997
- 1997-10-20 BR BR9712690-0A patent/BR9712690A/pt not_active IP Right Cessation
- 1997-10-20 DE DE59706904T patent/DE59706904D1/de not_active Expired - Fee Related
- 1997-10-20 AU AU50512/98A patent/AU5051298A/en not_active Abandoned
- 1997-10-20 WO PCT/EP1997/005777 patent/WO1998018806A1/de not_active Ceased
- 1997-10-20 JP JP10519998A patent/JP2001502716A/ja not_active Ceased
- 1997-10-20 US US09/297,241 patent/US6072052A/en not_active Expired - Fee Related
- 1997-10-20 CN CNB97180494XA patent/CN1146572C/zh not_active Expired - Fee Related
- 1997-10-20 AT AT97913164T patent/ATE215552T1/de not_active IP Right Cessation
- 1997-10-20 CA CA002269943A patent/CA2269943C/en not_active Expired - Fee Related
- 1997-10-20 HU HU9904497A patent/HUP9904497A3/hu unknown
- 1997-10-20 EP EP97913164A patent/EP0937094B1/de not_active Expired - Lifetime
- 1997-10-20 PT PT97913164T patent/PT937094E/pt unknown
- 1997-10-20 ES ES97913164T patent/ES2175377T3/es not_active Expired - Lifetime
- 1997-10-20 DK DK97913164T patent/DK0937094T3/da active
- 1997-10-20 KR KR10-1999-7003084A patent/KR100468206B1/ko not_active Expired - Fee Related

Also Published As

Publication number	Publication date
ES2175377T3 (es)	2002-11-16
EP0937094B1 (de)	2002-04-03
ATE215552T1 (de)	2002-04-15
KR100468206B1 (ko)	2005-01-26
CN1239965A (zh)	1999-12-29
DE19644050A1 (de)	1998-05-07
DK0937094T3 (da)	2002-07-15
DE59706904D1 (de)	2002-05-08
EP0937094A1 (de)	1999-08-25
WO1998018806A1 (de)	1998-05-07
AU5051298A (en)	1998-05-22
PT937094E (pt)	2002-09-30
HUP9904497A2 (hu)	2000-05-28
CA2269943A1 (en)	1998-05-07
BR9712690A (pt)	1999-10-19
HK1024485A1 (en)	2000-10-13
CN1146572C (zh)	2004-04-21
KR20000049018A (ko)	2000-07-25
US6072052A (en)	2000-06-06
HUP9904497A3 (en)	2000-11-28
JP2001502716A (ja)	2001-02-27

Legal Events

Date	Code	Title	Description
2002-07-19	EEER	Examination request
2009-10-20	MKLA	Lapsed

Publication	Publication Date	Title
EP2081882B1 (de)	2012-07-25	Hydroformylierungsverfahren
EP2131957B1 (de)	2013-06-12	Hydroformylierungsverfahren
US9108912B2 (en)	2015-08-18	Hydroformylation process
US20130158282A1 (en)	2013-06-20	Polyhedral oligomeric silsesquioxane (poss) bonded ligands and the use thereof
CN103772445B (zh)	2016-06-01	一种1,1’-二茂铁全氟烷基膦氮配体、其制备方法及应用
CA2269943C (en)	2006-12-12	Method for the production of ivermectin
US4613460A (en)	1986-09-23	Process for preparing α-L-aspartyl-L-phenylalanine methyl ester
CN102143968B (zh)	2014-07-02	制备阳离子铑络合物的方法
EP2516058B1 (de)	2013-12-18	Hydroformylierungsverfahren
US8779164B2 (en)	2014-07-15	Phosphine-based catalysts useful for the telomerization of butadiene
US5656748A (en)	1997-08-12	Process for the preparation of ivermectin
HK1024485B (en)	2005-02-18	Method for the production of ivermectin
CN111196777A (zh)	2020-05-26	一种布瓦西坦的合成制备
EP1151987A1 (de)	2001-11-07	Optisch aktive fluorierte binaphthol-derivate
JP4053325B2 (ja)	2008-02-27	ホスホニウム塩、その製造方法およびその用途
CN105037428A (zh)	2015-11-11	一种香豆素-3-膦酸酯衍生物的制备方法
US5051522A (en)	1991-09-24	Complex compound of rhodium-containing sulfonated triphenylphosphane
CA3074247A1 (en)	2019-03-07	Process for the preparation of ixazomib citrate
JP4183974B2 (ja)	2008-11-19	パラ−ジアリールホスフィノベンゼンスルホン酸塩の製造方法
CN110092802A (zh)	2019-08-06	一种制备曲贝替定中间体的方法
WO2002100872A1 (fr)	2002-12-19	P-diarylphosphinobenzenesulfonates de lithium, procede de preparation et utilisation de ces composes